Clear cell adenocarcinoma of urinary bladder and urethra: another urinary tract lesion immunoreactive for P504S

Arch Pathol Lab Med. 2008 Sep;132(9):1417-22. doi: 10.5858/2008-132-1417-CCAOUB.


Context: Clear cell carcinoma of the urinary bladder/ urethra is a rare tumor histologically resembling the neoplasms in the female genital tract. Adequate characterization of this tumor has been hampered by its rarity. alpha-Methylacyl-CoA racemase (AMACR)/P504S has been reported to be positive in prostatic adenocarcinoma, papillary renal cell carcinoma, and gastrointestinal neoplasmas; however, it has never been studied in clear cell carcinoma of the lower urinary tract.

Objective: To investigate the immunohistochemical staining profile in 4 primary clear cell carcinomas of the urinary tract, including P504S, which has not been previously evaluated in these tumors.

Design: Four cases of clear cell adenocarcinoma were retrieved from our archives: 2 cases from the urinary bladder (one each from a man and a woman) and 2 cases from the urethra (both from women, 1 in a diverticulum). Immunohistochemistry performed on the cases were P504S, K903, cytokeratin (CK) 7, CK20, CA 125, and p63.

Results: We found that clear cell carcinomas had a distinct immunoreactive profile: strongly positive for P504S, K903, and CK7, and negative for p63. Two cases were also positive for CA 125 and CK20.

Conclusion: The immunohistochemical profile of clear cell carcinomas shares some similarity to conventional urothelial carcinoma; however, it deviates from those tumors in being positive for P504S and negative for p63. This staining profile may suggest a nonurothelial origin for these tumors, may serve as a useful tool in the differential diagnosis of this tumor, and may reflect its etiology. Because similar expression of P504S is also seen in nephrogenic adenomas, this marker should not be used to differentiate nephrogenic adenomas from clear cell adenocarcinomas.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma, Clear Cell / metabolism*
  • Adenocarcinoma, Clear Cell / pathology
  • Aged
  • Biomarkers, Tumor / analysis*
  • CA-125 Antigen / biosynthesis
  • Female
  • Humans
  • Immunohistochemistry
  • Keratin-20 / biosynthesis
  • Keratin-7 / biosynthesis
  • Male
  • Membrane Proteins / biosynthesis
  • Middle Aged
  • Racemases and Epimerases / biosynthesis*
  • Urethral Neoplasms / metabolism*
  • Urethral Neoplasms / pathology
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology


  • Biomarkers, Tumor
  • CA-125 Antigen
  • CKAP4 protein, human
  • Keratin-20
  • Keratin-7
  • Membrane Proteins
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase